Cardiac glycosides (CGs) have been prescribed for centuries to treat congestive heart failure and arrhythmias, conditions in which they bind to the Na—K-ATPase and inhibit its activity. The number of CGs identified in animals and plants is growing and novel effects are becoming evident, including anti-cancer and anti-viral activities. While the anti-cancer effects have been confirmed in multiple studies, the anti-viral activities have not been well-studied. CGs were reported to inhibit HCMV replication at nM concentration and the present inventors have recently reported that digoxin, and ouabain are potent inhibitors of Towne HCMV replication. HCMV inhibition occurred at an early stage prior to DNA replication, but following binding to its cellular receptors.
Digoxin was reported to inhibit the growth of several cancer cells. A study of breast cancer patients showed that women taking digoxin had a significantly lower death rate compared to those not taking digitalis (6% vs. 34%, respectively). In addition, men who used digoxin regularly, especially users for ≥10 years, had a lower prostate cancer risk. Digoxin and ouabain have been reported to inhibit Herpes Simplex Virus 1 (HSV1) in nanomolar concentrations. Virus entry/attachment was not inhibited, but the expression of viral immediate-early (IE) and early genes was significantly reduced.
Despite recent research, there still exists an unmet need for development of novel anti-herpesvirus drugs which are relatively non-toxic and inhibit viral replication in the host.